There is strong support for the action of oxytocin as a physiological initiator of delivery in numerous species of mammals, including humans, but the mechanism by which oxytocin accelerates contraction of uterine muscle has not yet been clarified in sufficient detail. An analysis of the diverse research conducted recently on the mechanism of this action indicates that oxytocin manifests this effect in part by inducing direct contractions of the tunica muscularis of the uterus and in part by increasing the synthesis and release of contractile prostaglandins from the endometrium and deciduous membrane. Moreover, initiation of the process that leads to delivery is considered attributable to increased sensitivity of uterine muscle to oxytocin; i.e., initiation of the process leading to delivery is partially attributable to an increase in oxytocin receptors in uterine muscle.
The management of premature birth is a vital issue in the field of obstetrics. It is known that there is an increased number of oxytocin receptors in cases of premature birth or imminent abortion. Moreover, in the clinical setting, there is a substantial need for the capability to predict premature birth by measuring the expression level of oxytocin receptors and for developing drugs to suppress labor pains in premature birth. Oxytocin is also known to have lactogenic and hypertensive effects.
However, the mode of expression of oxytocin receptors in target tissues remains unclear, so these actions are not yet understood in sufficient detail. Moreover, with regard to another aspect of oxytocin, there are reports that levels of the substance in the blood are elevated in males at the time of ejaculation, and that oxytocin receptors are expressed in rat hippocampus tissue. However, the series of biological responses between oxytocin and oxytocin receptors has not yet been fully explained, and further clarification is needed in this area.
With respect to the above clinical and research requirements, one possibility is the use of anti-oxytocin receptor antibodies that specifically binds oxytocin receptors for the immunodetection of such oxytocin receptors. Recently, Kimura et al. cloned the cDNA of oxytocin receptors (Nature, 356, 526-529 (1992)) and clarified its primary structure. Based on this primary structure, these receptors were presumed to have the sevenfold-membrane-penetration-type secondary structure typical of G-protein-binding-type receptors. However, this reference did not teach the production of antibodies which specifically bind to the oxytocin receptor.
As discussed, the development of anti-oxytocin receptor antibodies is desirable for the purification and identification of recombinant oxytocin receptors, as well as for the rapid detection and identification of oxytocin receptors present in oxytocin-receptor-manifesting tissues.
However, there have as of yet, been no reports on antibodies which specifically bind to oxytocin receptors. Accordingly, the object of the present invention is to provide antibodies which specifically bind to oxytocin receptors.